A transcriptional regulatory role of the THAP11-HCF-1 complex in colon cancer cell
function.

Abstract

The recently identified Thanatos-associated protein (THAP) domain is an atypical zinc
finger motif with sequence-specific DNA-binding activity. Emerging data suggest that
THAP proteins may function in chromatin-dependent processes, including transcriptional
regulation, but the roles of most THAP proteins in normal and aberrant cellular processes
remain largely unknown. In this work, we identify THAP11 as a transcriptional regulator
differentially expressed in human colon cancer. Immunohistochemical analysis of human
colon cancers revealed increased THAP11 expression in both primary tumors and metastases.
Knockdown of THAP11 in SW620 colon cancer cells resulted in a significant decrease
in cell proliferation, and profiling of gene expression in these cells identified
a novel gene set composed of 80 differentially expressed genes, 70% of which were
derepressed by THAP11 knockdown. THAP11 was found to associate physically with the
transcriptional coregulator HCF-1 (host cell factor 1) and recruit HCF-1 to target
promoters. Importantly, THAP11-mediated gene regulation and its chromatin association
require HCF-1, while HCF-1 recruitment at these genes requires THAP11. Collectively,
these data provide the first characterization of THAP11-dependent gene expression
in human colon cancer cells and suggest that the THAP11-HCF-1 complex may be an important
transcriptional and cell growth regulator in human colon cancer.